Updates in juvenile dermatomyositis: pathogenesis and therapy

This review provides updates on juvenile dermatomyositis pathogenesis and treatment.

JDM pathogenesis research updates in genetic risk factors include C4 copy number. Studies clarify myositis-specific autoantibodies' (MSA) role in disease pathogenesis and more myositis-associated antibody (MAA) clinical associations. Recent studies validate an interferon (IFN)-regulated gene score and an IFN-related monocyte surface protein marker, SIGLEC-1. Vasculopathy and mitochondrial dysfunction evidence increases, both with ties to IFN. Studies point to not only T and B cells, but monocytes, macrophages, and neutrophils as dysregulated in JDM. Regarding treatment, there are growing reports of success with therapies targeting IFN-signaling (Janus kinase inhibitors), dazukibart (anti-IFN-beta), and anifrolumab (anti-IFNAR1). Chimeric antigen receptor (CAR) T-cell therapy targeting B-cells in a growing number of adult myositis patients and one JDM patient have dramatic reports of achieving drug-free remission.

Growing evidence show genetic markers, MSA, IFN, vasculopathy, varied immune cells, and mitochondrial dysfunction having important roles in JDM pathogenesis. Some refractory patients show benefit with newer IFN pathway-targeted therapies and cellular CAR-T-cell therapy. Further collaborative research on disease pathogenesis, treatment targets, and innovate clinical trial design is needed to increase access to more efficacious treatments in JDM.